International Journal of Nephrology and Renovascular Disease (May 2020)
Efficacy and Safety of Evocalcet Evaluated by Dialysate Calcium Concentration in Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis
Abstract
Takashi Shigematsu,1 Shinji Asada,2 Yuichi Endo,3 Takehisa Kawata,2,3 Masafumi Fukagawa,4 Tadao Akizawa5 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2Medical Affairs Department, Kyowa Kirin Co., Ltd., Tokyo, Japan; 3R&D Division, Kyowa Kirin Co., Ltd., Tokyo, Japan; 4Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan; 5Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, JapanCorrespondence: Takashi ShigematsuDepartment of Nephrology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, JapanTel +81-73-441-0638Fax +81-73-441-0639Email [email protected]: Evocalcet is a novel oral calcimimetic drug that has demonstrated similar efficacy to cinacalcet in regulating serum parathyroid hormone (PTH), calcium, and phosphate levels, with fewer upper gastrointestinal tract-related adverse drug reactions (ADRs) in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. We investigated the efficacy and safety of once-daily oral evocalcet under different dialysate calcium concentrations.Patients and Methods: A post hoc analysis by dialysate calcium concentration (2.5, 2.75, and 3.0 mEq/L) was performed using data from a previous Phase 3 study that included cinacalcet as an active control. Efficacy endpoints were the proportion of patients who achieved the target intact PTH levels of ≥ 60 and ≤ 240 pg/mL between Week 28 and Week 30; time-course changes in serum intact PTH; calcium and phosphorus levels, bone turnover markers, and fibroblast growth factor 23 (FGF23) over the 30-week study period. Safety endpoints were overall ADRs and hypocalcemia- and upper gastrointestinal tract-related ADRs.Results: A total of 634 patients were included in the analysis. Levels of intact PTH, calcium, phosphate, bone turnover markers, and FGF23 showed improvement in all sub-groups, irrespective of dialysate calcium concentration. The incidence of upper gastrointestinal tract-related ADRs was significantly lower in the evocalcet group than the cinacalcet group with dialysate calcium concentrations of 2.75 and 3.0 mEq/L (p< 0.05 for both concentrations).Conclusion: Evocalcet was effective and safe in regulating the levels of serum intact PTH, calcium, and phosphate in patients with secondary hyperparathyroidism undergoing hemodialysis, irrespective of dialysate calcium concentration.Keywords: hypocalcemia, intact parathyroid hormone, oral calcimimetic, post hoc analysis, upper gastrointestinal tract
